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for the Fr1da Study Group IMPORTANCE Public health screening for type 1 diabetes in its presymptomatic stages may reduce disease severity and burden on a population level.OBJECTIVE To determine the prevalence of presymptomatic type 1 diabetes in children participating in a public health screening program for islet autoantibodies and the risk for progression to clinical diabetes.DESIGN, SETTING, AND PARTICIPANTS Screening for islet autoantibodies was offered to children aged 1.75 to 5.99 years in Bavaria, Germany, between 2015 and 2019 by primary care pediatricians during well-baby visits. Families of children with multiple islet autoantibodies (presymptomatic type 1 diabetes) were invited to participate in a program of diabetes education, metabolic staging, assessment of psychological stress associated with diagnosis, and prospective follow-up for progression to clinical diabetes until July 31, 2019. EXPOSURES Measurement of islet autoantibodies.MAIN OUTCOMES AND MEASURES The primary outcome was presymptomatic type 1 diabetes, defined by 2 or more islet autoantibodies, with categorization into stages 1 (normoglycemia), 2 (dysglycemia), or 3 (clinical) type 1 diabetes. Secondary outcomes were the frequency of diabetic ketoacidosis and parental psychological stress, assessed by the Patient Health Questionnaire-9 (range, 0-27; higher scores indicate worse depression; Յ4 indicates no to minimal depression; >20 indicates severe depression). RESULTSOf 90 632 children screened (median [interquartile range {IQR}] age, 3.1 [2.1-4.2] years; 48.5% girls), 280 (0.31%; 95% CI, 0.27-0.35) had presymptomatic type 1 diabetes, including 196 (0.22%) with stage 1, 17 (0.02%) with stage 2, 26 (0.03%) with stage 3, and 41 who were not staged. After a median (IQR) follow-up of 2.4 (1.0-3.2) years, another 36 children developed stage 3 type 1 diabetes. The 3-year cumulative risk for stage 3 type 1 diabetes in the 280 children with presymptomatic type 1 diabetes was 24.9% ([95% CI, 18.5%-30.7%]; 54 cases; annualized rate, 9.0%). Two children had diabetic ketoacidosis. Median (IQR) psychological stress scores were significantly increased at the time of metabolic staging in mothers of children with presymptomatic type 1 diabetes (3 [1-7]) compared with mothers of children without islet autoantibodies (2 [1-4]) (P = .002), but declined after 12 months of follow-up (2 [0-4]) (P < .001).CONCLUSIONS AND RELEVANCE Among children aged 2 to 5 years in Bavaria, Germany, a program of primary care-based screening showed an islet autoantibody prevalence of 0.31%. These findings may inform considerations of population-based screening of children for islet autoantibodies.

OBJECTIVE -To give an up-to-date profile of nephropathy and the involvement of risk factors in a large, prospective cohort of patients with type 1 diabetes and largely pediatric and adolescent onset of disease. RESEARCH DESIGN AND METHODS-A total of 27,805 patients from the nationwide, prospective German Diabetes Documentation System survey were included in the present analysis. Inclusion criteria were at least two documented urine analyses with identical classification. Urine analyses, treatment regimens, diabetes complications, and risk factors were recorded prospectively. Baseline characteristics were age at diagnosis 9.94 years (median [interquartile range 5.8 -14.3]), age at last visit 16.34 years (12.5-22.2), and follow-up time 2.5 years (0.43-5.3). Cumulative incidence of nephropathy was tested by Kaplan-Meier analysis and association with risk factors by logistic regression.RESULTS -Nephropathy was classified as normal in 26,605, microalbuminuric in 919, macroalbuminuric in 78, and end-stage renal disease (ESRD) in 203 patients. After calculated diabetes duration of 40 years, 25.4% (95% CI 22.3-28.3) had microalbuminuria and 9.4% (8.3-11.4) had macroalbuminuria or ESRD. Risk factors for microalbuminuria were diabetes duration (odds ratio 1.033, P Ͻ 0.0001), A1C (1.13, P Ͻ 0.0001), LDL cholesterol (1.003, P Ͻ 0.0074), and blood pressure (1.008, P Ͻ 0.0074), while childhood diabetes onset (1.011, P Ͻ 0.0001) was protective. Male sex was associated with the development of macroalbuminuria.CONCLUSIONS -Diabetes duration, A1C, dyslipidemia, blood pressure, and male sex were identified as risk factors for nephropathy. Therefore, besides the best possible metabolic control, early diagnosis and prompt treatment of dyslipidemia and hypertension is mandatory in patients with type 1 diabetes. Diabetes Care 30:2523-2528, 2007M icro-and macroalbuminuria are important markers for early and progressive diabetic kidney disease. Patients with type 1 diabetes face a 20 -50% probability of developing endstage renal disease (ESRD) requiring dialysis or renal transplantation (1). But over the last decades, cumulative incidence of nephropathy has further declined, which was attributed to intensified treatment regimens and a more aggressive therapy of hypertension and dyslipidemia (1,2).Since the 1980s, microalbuminuria has been established as an early marker of progressive kidney disease in diabetes (3), starting at pediatric age (4,5), and currently albumin excretion rate (AER) remains the best available noninvasive predictor for diabetic nephropathy and should be measured regularly according to established guidelines (6 -8).Since the Diabetes Control and Complications Trial (DCCT), glycemic control was established as the dominant risk factor for the development of diabetic nephropathy (9). Moreover, the DCCT follow-up Epidemiology of Diabetes Interventions and Complications study has demonstrated a persistent delay of progression of diabetic nephropathy 7-8 years after the end of the DCCT, in the previously intensively trea...

Using a trajectory approach, we determined five distinct longitudinal patterns of glycemic control from childhood to early adulthood. Diabetes self-care, treatment differences, and demographics were related to different HbA courses.

IntroductionType 1 diabetes can be diagnosed at an early presymptomatic stage by the detection of islet autoantibodies. The Fr1da study aims to assess whether early staging of type 1 diabetes (1) is feasible at a population-based level, (2) prevents severe metabolic decompensation observed at the clinical manifestation of type 1 diabetes and (3) reduces psychological distress through preventive teaching and care.Methods and analysisChildren aged 2–5 years in Bavaria, Germany, will be tested for the presence of multiple islet autoantibodies. Between February 2015 and December 2016, 100 000 children will be screened by primary care paediatricians. Islet autoantibodies are measured in capillary blood samples using a multiplex three-screen ELISA. Samples with ELISA results >97.5th centile are retested using reference radiobinding assays. A venous blood sample is also obtained to confirm the autoantibody status of children with at least two autoantibodies. Children with confirmed multiple islet autoantibodies are diagnosed with pre-type 1 diabetes. These children and their parents are invited to participate in an education and counselling programme at a local diabetes centre. Depression and anxiety, and burden of early diagnosis are also assessed.ResultsOf the 1027 Bavarian paediatricians, 39.3% are participating in the study. Overall, 26 760 children have been screened between February 2015 and November 2015. Capillary blood collection was sufficient in volume for islet autoantibody detection in 99.46% of the children. The remaining 0.54% had insufficient blood volume collected. Of the 26 760 capillary samples tested, 0.39% were positive for at least two islet autoantibodies.DiscussionStaging for early type 1 diabetes within a public health setting appears to be feasible. The study may set new standards for the early diagnosis of type 1 diabetes and education.Ethics disseminationThe study was approved by the ethics committee of Technische Universität München (Nr. 70/14).